Pain experience has both sensory and affective dimensions. Current drugs for pain and pain-induced negative psychological disorders have limited efficacy and unwanted side effects. An ideal therapeutic modality should treat sensory and affective pain simultaneously with few side effects. Studies have demonstrated that electroacupuncture (EA), which has few or no adverse effects, significantly inhibits hyperalgesia, the sensory discriminative dimension of pain, but its effects on the affective dimension have not been tested. Previous studies show that opioids and NMDA receptors in the anterior cingulate cortex (ACC) are involved in affective responses. The objective of this study is to evaluate the effects and mechanisms of EA on pain-induced affective behavior. The hypothesis is that EA inhibits affective response by activating endogenous opioids and inhibiting NR1 phosphorylation in the ACC. We will use an animal model of peripheral CFA (complete Freund adjuvant)-induced affective response, assessed with a conditioned place avoidance (CPA) test, recently established in our lab to mimic the emotional responses of patients with pain. The aims are: Aim I: Evaluate the effects of EA on pain-induced affective response. EA at 10 or 100 Hz, 20 min and 3 mA, the maximum current intensity tolerated by rats, will be used at acupoint GB30 (Huan Tiao) to study how EA influences a rat model of affective response. We hypothesize that EA will significantly inhibit this response. Aim II: Determine whether opioids mediate EA inhibition of affective response. The involvement of opioids in EA action will be determined by administering selective mu, delta and kappa opioid receptor antagonists to the ACC. We hypothesize that these antagonists will prevent EA inhibition of affective response. Aim III: Determine whether EA inhibits phosphorylation of NR1, the essential subunit of NMDA receptor, and its modulation by opioids in the ACC. Rats with and without opioid receptor antagonist pretreatment will be treated with EA. We will examine NR1 phosphorylation levels using western blot. We hypothesize that EA will significantly inhibit NR1 phosphorylation, and that opioid receptor antagonist pretreatment will block this effect. The findings of this study will advance our understanding of the influence of EA treatment on the affective dimension of pain. The success of the study will provide important information for a clinical trial on the affective dimension of pain and has the potential of greatly advancing pain management. PUBLIC HEALTH RELEVANCE: Pain procession is consisted of sensory and affective dimensions. Inadequate control and management of pain remain serious problems. Previous studies have demonstrated that electroacupuncture (EA) significantly inhibits hyperalgesia, the sensory dimension. Whether EA modulate the affective dimension has not been investigated. This study will evaluate the effects and mechanisms of EA on affective dimension. The findings will advance our knowledge of EA treatment on affective dimensions of pain. The success of this study will provide important information for a clinical trial and finally greatly advance the management of pain.